GEO series
CD137 agonism enhances anti-PD1 induced activation of clonally expanded CD8+ T cells in a neoadjuvant pancreatic cancer clinical trial
GSE279781
Homo sapiens
Expression profiling by high throughput sequencing; Other
30 samples
Submitted 2024/12/16
Platform GPL24676
Summary
Successful pancreatic ductal adenocarcinoma (PDAC) immunotherapy requires therapeutic combinations that induce quality T cells. Tumor microenvironment (TME) analysis following therapeutic interventions can identify response mechanisms to guide design of more effective combinations. We provide a reference single-cell dataset from PDAC-infiltrating T cell and monocyte subsets from a human neoadjuvant clinical trial comparing the granulocyte-macrophage colony-stimulating factor (GM-CSF)-secreting allogeneic PDAC vaccine GVAX alone, in combination with anti-PD1, or with both anti-PD1 and a CD137 agonist. Tumor infiltrating leukocytes analyzed two weeks post neoadjuvant therapy revealed shifts in CD8+ T cell activation as well as cytoskeletal and extracellular matrix (ECM)-interacting components with Cy/GVAX and anti-PD1. Addition of a CD137 agonist was associated with increased abundance of activated and clonally expanded CD8+ T cells with distinct perturbations in cytoskeletal and ECM components. Furthermore, a new computational method to compare ligand-receptor networks between patients from different treatment arms found that CD137 agonism is associated with immunosuppressive TREM2 signaling in tumor associated macrophages (TAMs) that corresponds to changes in cell metabolism, function, and ECM interactions. Altogether these findings associate therapy with GVAX, anti-PD1, and CD137 agonist with enhanced CD8+ T cell function while inducing alternative immunosuppressive pathways in patients with PDAC.
Published in
Montagne JM, Mitchell JT, Tandurella JA et al.
· iScience 2025
· PMID 39811671
· doi:10.1016/j.isci.2024.111569
This dataset
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Direct links to NCBI, no account and no request form: the whole study as GSE279781_RAW.tar, processed values as the series matrix, the supplementary file directory, and per-sample supplementary files for any of the 30 samples. Raw sequencing reads are also available from ENA.
Also filed as BioProject PRJNA1174340. Searching any of these in the dataset finder brings you back here.
Study design
30 conditions, each sampled once — no replicated groups
Read from 30 sample titles: 30 distinct titles with little repetition. Check it against the sample list below before relying on it.
Samples in this study
0 selected
- GSM8580060 14_P-45_TIL (scTCR-seq)
- GSM8580061 11_P-44_TIL (scTCR-seq)
- GSM8580062 12_P-2_TIL (scTCR-seq)
- GSM8580063 13_P-42_TIL (scTCR-seq)
- GSM8580064 3_P-6_TIL (scTCR-seq)
- GSM8580065 4_P-20_TIL (scTCR-seq)
- GSM8580066 5_P-33_TIL (scTCR-seq)
- GSM8580067 1_P-24_TIL (scTCR-seq)
- GSM8580068 10_P-32_TIL (scTCR-seq)
- GSM8580069 2_P-17_TIL (scTCR-seq)
- GSM8580070 6_P-3_TIL (scTCR-seq)
- GSM8580071 7_P-25_TIL (scTCR-seq)
- GSM8580072 8_P-23_TIL (scTCR-seq)
- GSM8580073 15_P-46_TIL (scTCR-seq)
- GSM8580074 16_P-40_TIL (scTCR-seq)
- GSM8580075 14_P-45_TIL (scRNA-seq)
- GSM8580076 11_P-44_TIL (scRNA-seq)
- GSM8580077 12_P-2_TIL (scRNA-seq)
- GSM8580078 13_P-42_TIL (scRNA-seq)
- GSM8580079 3_P-6_TIL (scRNA-seq)
- GSM8580080 4_P-20_TIL (scRNA-seq)
- GSM8580081 5_P-33_TIL (scRNA-seq)
- GSM8580082 1_P-24_TIL (scRNA-seq)
- GSM8580083 10_P-32_TIL (scRNA-seq)
- GSM8580084 2_P-17_TIL (scRNA-seq)
- GSM8580085 6_P-3_TIL (scRNA-seq)
- GSM8580086 7_P-25_TIL (scRNA-seq)
- GSM8580087 8_P-23_TIL (scRNA-seq)
- GSM8580088 15_P-46_TIL (scRNA-seq)
- GSM8580089 16_P-40_TIL (scRNA-seq)
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